Excessive expression or lack of effective enzymes often lead to metabolism or gastro-intestinal illnesses. Imbalance of the lipase level can, for example, cause a multitude of digestion illnesses, including the malabsorption of fat. For patients who suffer from mucoviscidosis, chronic pancreatitis and other pancreatic illnesses, fat malabsorption does occur. Commonly observed consequences of fat malabsorption are abdominal pain, steatorrohoea (fat diarrhoea), lack of essential fat acids, of fat-soluble vitamins (for example A, D, E and K) and general developmental disorders.
The usual procedure for the treatment of illnesses with lipase insufficiency are orally administered lipase enzymes, most products on the base of porcine pancreas which has been unfatted, dried and crushed. The corresponding product consists of several enzymes such as lipase, amylases, proteases, esterases etc.
Generally available administering forms are usually tablets, micro-tablets, micro-dragees, capsules, powder and granules coated with a film resistant to gastric juice. The disadvantage of these administering forms consists in the discomfort of the administering to patients who have to swallow big tablets or capsules. In particular in the case of patients who are not able to swallow tablets such as small children or who need artificial feeding, these administration forms can be applied only with difficulties. The crushing of the tablets cannot assure any homogeneous distribution of the enzymes to the chymus and the low solubility of the product can lead to the occlusion of the feeding tube.
Liquid formulations of digestion enzymes have been described for example in EP 0826375 or US 2006/0128587. In these patent applications the enzymes are stabilized either with additives, or by modification of the enzymes. However, in both cases, the enzyme solutions have to be prepared fresh before administration which is less convenient than a ready-made liquid preparation. Moreover, the effects of additives on the active substance, on the effectiveness and the safety should be considered.
The treatment on the base of easily available pancreatinic preparations has various disadvantages. The lipase is considered as the main enzyme. Because of the low specific lipase activity a quantity of up to 5-10 g per day has to be taken by the patient. Moreover, the porcine lipase is active in a pH range of 5 to 9 and is thus inactive during the passage through the stomach.
Moreover, the lipase activity has to be protected from the acid pH conditions in the stomach because of its sensitivity to a low pH value, for example by a coating of the tablets resistant to gastric juice. In a few medical applications, the accompanying proteolytic or amylolytic enzyme activities are not desired. The amylase content is not desired for children with mucoviscidosis while lipase is therapeutically necessary. Proteases are contraindicated for patients with acute pancreatitis or active phases of chronic pancreatitis (see U.S. Pat. No. 5,645,832). Thus, the availability of a lipase as single protein is advantageous. In U.S. Pat. No. 5,645,832 or U.S. Pat. No. 5,489,530 a lipase obtained from bacteria has already been described in detail. Apart from the making available of a purified single protein, the lipase concentration of bacterial lipase is very high so that only low preparation quantities (approx. 0.2 g) have to be administered. The pH value for the activity of the bacterial lipase is situated between 3 and 9 and thus overcomes the limitations of the stability and activity of porcine lipase/pancreatin. This means that the lipolytic effect of bacterial lipase can be applied with a better effect in the gastrointestinal tract than the products for the therapy of digestion disorders commonly sold on the market. Additionally, the bacterial lipase is a non-animal product which avoids the risk of possible viral infection originating from animal sources.